Ipilimumab for advanced melanoma in the real world: The Northern Ireland experience

Abstract

Background: Ipilimumab was the first immune checkpoint inhibitor to demonstrate a survival benefit for metastatic melanoma patients and has been available in Northern Ireland (NI) since 2012. With the advent of more novel checkpoint inhibitor options and combinations, single-Agent Ipilimumab use has declined, but evidence indicates it may continue to have a role after PD-1 inhibitor monotherapy failure. We investigated our clinical outcomes in the earlier era of this treatment. Method(s): Ipilimumab-Treated patient data were retrospectively collected using electronic record systems and clinical notes. Descriptive and inferential statistics using Microsoft ExcelVR and SPSSVR were employed to evaluate outcomes, including objective response rates (RR) according to RECIST criteria, disease control rates (DCR), progression free survival (PFS) and overall survival (OS). Result(s): 70 patients were treated with Ipilimumab in NI between November 2012 and December 2015. 57 patients had a cutaneous or unknown primary, and of these, 40.3% harboured a BRAF mutation. 56.4% of all patients had received prior systemic therapy. Median follow-up duration was 12 months (range 0.63 to 51.2 months), and median number of cycles administered was 4, with 65.7% completing 4 cycles. RR and DCR were 10.1% and 31.9% respectively, and the median PFS was 2.9 months and OS 11.7 months. 50.7% of patients with disease progression received subsequent systemic therapy but 52% of deaths occurred prior to access to PD-1 inhibitor and BRAF/MEK targeted therapy in NI. Grade 3-4 toxicities occurred in 31.4% of patients. The 30-day mortality was 5.7% (4 patients), with only 1 suspected treatment-related death. Serum LDH>upper limit of normal, serum neutrophil:lymphocyte ratio>4, M1c disease, uveal primary, presence of brain metastases and ECOG performance status 2 were identified as clinical factors which correlate with worse PFS and OS, and all early mortality cases had two or more of these factors. Conclusion(s): Efficacy and toxicity data, and prognostic indicators for our cohort, are similar to other published data. Ipilimumab is deliverable in a non-clinical trial setting with acceptable outcomes, and may remain relevant as a viable treatment option. Patient selection is key to optimal results.